LAUSR

To the Editor, I have read with great interest the article by Lei et al.—it has been an edifying experience to come across such a clinically relevant and important research where the authors have sought to evaluate antifibrinolytic and anti-inflammatory effects of high initial-dose of tranexamic acid (TXA) in total knee arthroplasty (TKA). They have demonstrated favourable effect of the regimen comprising high pre-operative dose of intravenous (IV)-TXA (60 mg/kg) in reducing blood loss, inhibition of fibrinolytic, and inflammatory activity, with added benefit of better pain control without additional risk of complications compared to lower initial dose of IV-TXA (20 mg/kg) regimen; authors deserve applause for this novel study [1]. However, there are few comments I would like to put forth, which I believe are pertinent to the subject of this study. Tranexamic acid (TXA), as a blood-conserving agent in total knee or hip arthroplasty, has been studied extensively in the last few years; reason for this scientific discourse stems from the fact that definitive guideline of TXA administration like formulation, dosage, and timing still remains elusive. Although considered safe, theoretical risk of thromboembolism cannot be denied, since most studies are underpowered to detect this relatively rare complication. Ambiguities and inconsistencies abound in the literature concerning the most efficacious and safest route of TXA administration in TKAs—whether it is IV, intra-articular (IA), oral or combined (IV+IA). However, it is generally agreed that if one is to elect a single and safest dose regimen, then topical TXA (IA) appears attractive, since it shows the lowest risk ratio for venous thrombosis [2]. Against this backdrop, the recent study by Lei et al. has favoured protocol of multiple dose of IV-TXA for TKAs starting with high initial pre-operative dose (60 mg/kg) followed by five doses of 1 g TXA at three, six, 12, 18, and 24 hours after the first dose [1]. However, they excluded patients with cardiovascular and cerebrovascular morbidities, renal or hepatic dysfunction, and patients having previous history of venous thrombosis. Quite naturally, it remains to be established whether this high dose regimen is practical and safe in the presence of risk factors, since a sizeable proportion of patients needing TKAs present with multiple co-morbidities. Until more concrete evidences regarding safety and efficacy are available at our armamentarium, I believe a bit circumspection is deemed paramount before adopting a high dose regimen for patients undergoing TKAs, especially for those with risk factors and multiple co-morbidities. Another concern that needs further appraisal is the costbenefit ratio; two recent meta-analyses have demonstrated no additional benefit, in reducing blood loss or transfusion requirement, with high and/or repeated dose of TXA; it was regarded as unnecessary, and avoiding additional dose leads to less drug exposure and cost saving benefits [2, 3]. It is therefore imperative to ponder whether it is too much of drugs with the high-dose regimen and repeated post-operative administrations, when satisfactory blood conservation in TKAs has been substantiated with seemingly safer and more convenient brethren of only topical (IA) or only single IV or combined (pre-operative IV + IA) TXA administration [2, 4–7]. Since much of our efforts are now being directed towards improving patients’ satisfaction and reducing unwarranted morbidities after TKAs, it seems logical to practice a rational approach to safeguard patients’ well-being with established alternative regimen available at surgeons’ disposal until more studies emanate to dispel the lingering concerns. All the patients in this study had unilateral primary TKAs without tourniquet. It is unclear whether all were operated upon by single surgeon, since amount of blood loss is also contingent on surgeon-related factors like expertise and * Saubhik Das [email protected]